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Increased IgG Levels at Diagnosis Are Associated With Worse Prognosis of Patients With Primary Biliary Cholangitis
Eirini I Rigopoulou1,2, Vassiliki Lygoura1,2, Stella Gabeta1,2
1Department of Medicine and Research Laboratory of Internal Medicine, National Expertise Center of Greece in Autoimmune Liver Diseases, General University Hospital of Larissa, Larissa, Greece.
Background And Aim:
A proportion of patients with primary biliary cholangitis (PBC) have increased IgG (I-IgG) levels at baseline, though not fulfilling the criteria of autoimmune hepatitis/PBC variant. Our aim was to evaluate whether I-IgG has prognostic significance in non-cirrhotic PBC patients.
Methods:
Retrospective analysis of prospectively collected data from 675 PBC patients (592 non-cirrhotic) with available IgG levels at first evaluation was performed.
Results:
Among non-cirrhotic patients, 97 with I-IgG were more frequently females (p < 0.05), having a higher frequency of concurrent autoimmune diseases (p = 0.01) and a higher frequency of PBC-specific ANA (p < 0.001), sp100 (p < 0.001) and gp210 (p = 0.029) compared to 495 with normal IgG (N-IgG). Patients with I-IgG were older (p < 0.001) and had lower albumin (p < 0.001) and higher AST (p < 0.001), ALT (p = 0.005), ALP (p = 0.006), γGT (p = 0.038) and IgM (p < 0.001) compared to those with N-IgG. I-IgG patients had a higher probability of cirrhosis development (Breslow p < 0.001; log-rank p = 0.05) and liver-related death (Breslow p = 0.034; log-rank p < 0.05) compared to N-IgG patients. IgG > 1.5xULN was the highest risk factor for cirrhosis development (HR = 9.507, 95% CI: 1.221-74.038, p = 0.032) and liver-related death (HR = 27.140, 95% CI: 3.111-236.783; p = 0.003); IgG normalisation after 1 year of UDCA treatment had a favourable effect on disease outcome. Ν-IgG was associated with a higher probability of liver stiffness regression (p = 0.025).
Conclusions:
This long-term study demonstrates that I-IgG levels characterise a subgroup of non-cirrhotic PBC patients with faster disease progression and increased probability of liver-related death. Normalisation of IgG levels during UDCA treatment seems to improve prognosis and therefore, these patients could benefit from stricter follow-up and earlier add-on second-line treatments.
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